The versatile England international started for Pep Guardiola's holders against Young Boys BSC in the Champions League on Tuesday night, but was replaced by Nathan Ake at half-time of a one-sided 3-0 victory in Group G that saw the dominant holders qualify for the last 16 of Europe's elite club competition for the 11th successive season with two matches to spare as they also set a new English record by extending their long unbeaten run on the continent.
While City did not feel Stones' absence against the hopelessly overmatched Swiss champions, it will likely be more keenly felt moving forward as City travel to Chelsea before the international break before consecutive home games against Premier League title rivals Liverpool and Tottenham coming up in late November and early December.
City were also forced into a very late change ahead of kick-off against Young Boys, with Manuel Akanji said to be feeling ill as he was replaced in the starting lineup by Kyle Walker.
However, Guardiola now appears to have confirmed that the Switzerland defender is actually being troubled by a back issue.
"Manuel had a problem in the back, it was block," the City boss told TNT Sports at the Etihad Stadium on Tuesday. "And when this happens, it is out.
"And unfortunately John felt again, so. I feel so sorry for him because he is so professional and committed.
"It is a big loss for us. John is so important with what he does. Recover and the season is long, we'll be back stronger."
Pressed on if he expects Stones to be out for a while, Guardiola responded: "Yeah, I think so."